We have developed a highly sensitive and specific method for quantitative analysis of the prealbumin variant in the sera of FAP patients by using radioimmunoassay for a nonapeptide corresponding to subsequence [22-30] of the prealbumin variant.
These results suggest that factors other than the rate of transfer of the variant form prealbumin from plasma to an extravascular compartment may play a critical role in the pathogenesis of amyloid deposition in FAP patients.
Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant genetic disease, and the major component of the amyloid fibrils from FAP patients was shown to be variants of transthyretin (TTR) with single amino acid substitutions.
Polymorphic analysis of the length of the Cfr13 I-restriction fragment confirmed the base change, and made it possible to detect the mutant TTR Gly42 gene in the FAP subjects.
The level of the variant TTR (methionine instead of valine at position 30) in his serum was much higher than that usually found in type I FAP patients.
This is the first FAP family of Taiwanese origin demonstrating a causative gene abnormality, and FAP with TTR-Pro55 was considered to be more serious compared with other forms of FAP.
We studied the haplotypes of 27 families (24 French, 2 British and 1 Greek) with FAP met 30 by analysing three polymorphisms in introns of the TTR gene.
Several TTR variants have been reported in association with familial amyloid polyneuropathy (FAP) and the characterization of the mutations is crucial for understanding the process of amyloidogenesis.
In addition, we have characterized the Thr-119-MetTTR variant, which is a common nonpathogenic variant in the Portuguese population, to further investigate the role that this mutation plays in protecting individuals who also carry the Val-30-Met mutation against the classically severe FAP pathology.
We propose an approach to molecular diagnosis in European patients with FAP, apart from members of families with known mutations, based on the frequency of TTR mutations observed in this and and other studies of FAP in Europe.